Antigenotoxicity and Cytotoxic Potentials of Metabiotics Extracted from Isolated Probiotic, Lactobacillus rhamnosus MD 14 on Caco-2 and HT-29 Human Colon Cancer Cells.

Probiotics, the beneficial bacteria produce active metabolites which could probably mimic their anticancer effect and prevent the risk associated with live bacteria. Thus, the study was designed to isolate effective lactic acid bacteria (LAB) and monitor anticancerous potential of their metabiotic extracts. Probiotics were isolated from different sources and their cell free supernatants (CFS) were screened for antigenotoxic and cytotoxic potentials using SOS Chromo Test and MTT assay on Caco-2 and HT-29 cells. Organic extracts of CFS were prepared and dissolved in different solvents. The isolate with most effective metabiotic extract in terms of cytotoxicity was classified for probiotic and phylogenetic characters and the metabiotic extract was characterized physiochemically. Among 60 isolated LAB, CFS of only 10 isolates showed antigenotoxicity more than 30% and four exhibited 70-80% cytotoxicity. Further, organic extracts of these four CFS dissolved in carboxymethyl cellulose showed 80-90% cytotoxicity. Interestingly, the most effective isolate was found to possess probiotic attributes and phylogenetic characterization revealed it to be Lactobacillus rhamnosus MD 14. Physiochemical characterization of its metabiotic extract indicated the presence of heat sensitive organic acids and proteins. To conclude, metabiotics produced by isolated probiotic L. rhamnosus MD 14 exhibited both antigenotoxic and cytotoxic potential against colon cancer.

Prophylactic intervention of probiotics (L.acidophilus, L.rhamnosus GG) and celecoxib modulate Bax-mediated apoptosis in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

BACKGROUND: Colorectal cancer has been found to be attenuated either with prophylactic manipulation of gut microbiome with probiotics or celecoxib, a non-steroidal anti-inflammatory drug mainly by suppressing early pro-carcinogenic markers in various experimental studies. Therefore, the present study was designed to assess the prophylactic potential of combinatorial administration of probiotics (Lactobacillus rhamnosus GG, Lactobacillus acidophilus) and celecoxib in experimental colon carcinogenesis. METHODS: Six groups of Spraugue Dawely rats received probiotics L.rhamnosus GG or/and L.acidophilus in combination with celecoxib one week prior to the inducement of tumor by 1,2-dimethylhydrazine (DMH) and the treatment continued for 18 weeks. Prophylactic potentials of probiotics and celecoxib were determined by employing various methods such as tumor incidence, tumor burden, tumor multiplicity, apoptosis, caspase activity, expression of proto-oncogene K-ras and tumor suppressor p53 gene in colonic tumors. RESULTS: Interestingly, it was found that one week prior supplementation of both probiotics and celecoxib reduced tumor burden, tumor multiplicity, down-regulated the expression of anti-apoptotic Bcl-2, proto-oncogene K-ras and up-regulated pro-apoptotic Bax as well as tumor suppressor p53 in L.rhamnosus GG + celecoxib+DMH animals compared with counter controls and DMH-treated. CONCLUSIONS: It can be concluded that such combinatorial approach may be useful in reducing the burden and severity of disease in highly susceptible individuals but needs to be validated clinically.

[NH3(CH2)4NH3]SnX4 (X = Br, I): Dion-Jacobson type 2-D perovskites with short interlayer spacing.

Two-dimensional tin(II) halide perovskites stand as an environmentally benign alternative to Pb(II) halide perovskites. However, they are often challenging to make due to the oxidation of Sn(II) ion to more stable Sn(IV) ion. Here we report hybrid tin bromide and iodide perovskites: (1,4-BDA)Sn(IV)Br6 and (1,4-BDA)Sn(II)X4 (where X = Br, I; 1,4-BDA = 1,4-diammoniumbutane) with 0D and 2D structures, respectively. Their synthesis, structural characterization and photophysical properties are reported. They show bandgaps in the 1.94-2.70 eV range.

Assessing the Relationship Between COVID-19 and Dental Decay Risk in Youth: A Retrospective Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted public health globally, with particular attention on the effects on children, adolescents, and young adults. This study aimed to investigate the potential relationship between COVID-19 and caries risk in this age group. METHODS: A retrospective chart review was conducted on 120 patients between the ages of six and 25 years who received dental treatment at a university-affiliated dental clinic between January 2020 and December 2021. Demographic and medical data were collected, and dental examinations were performed to record the number of decayed, missing, and filled teeth (DMFT) and decayed, missing, and filled surfaces (DMFS). Data were analyzed using descriptive statistics, chi-square test or Fisher's exact test, student's t-test or Mann-Whitney U test, and multivariate regression analysis. RESULTS: Of the 120 patients, 40 were COVID-19-positive, and 32 of those patients were at high caries risk. Of the 80 patients who were COVID-19 negative, 48 were at high caries risk. There was a statistically significant association between COVID-19 exposure and caries risk. Participants who tested positive for COVID-19 had 1.8 times higher odds of dental caries than those who tested negative. However, no significant association was found between caries risk and age, gender, or previous dental history. CONCLUSION: The findings suggest that COVID-19 may be a risk factor for caries in children, adolescents, and young adults. Dental professionals should consider COVID-19 exposure as a potential risk factor when assessing caries risk in this age group. Further research is needed to better understand the mechanism underlying this association.

Insulin and leptin oscillations license food-entrained browning and metabolic flexibility.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Heat transfer and hydraulics for a novel receiver pipe of solar parabolic trough: a computational approach.

The effect of symmetrical convex-concave corrugations on receiver pipe of a parabolic trough solar collector is numerically investigated. Twelve distinct geometrically configured receiver pipes with corrugations have been examined for this purpose. The computational study is conducted for varying corrugation pitch (4 mm to 10 mm) and height (1.5 mm to 2.5 mm). Heat transfer enhancement, flow behavior, and overall thermal performance of fluid moving through a pipe under non-uniform heat flux condition are all determined in this work. The Reynolds number ranges from 5000 to 50,000. The findings reveal that presence of corrugations leads to axial whirling and vortices in the receiver pipe, thus enhancing the heat transfer. The receiver pipe having corrugations of 8 mm pitch and 2 mm height gave the best results. The maximum enhancement in average Nusselt number over smooth pipe has been observed as 28.51%. In addition, relationships of Nusselt number and friction factor against selected design parameters and operating conditions are also displayed as correlations.

An Assessment of the Prevalence of Dental Caries, Oral Hygiene Status, Deft Index, and Oral Hygiene Habits Among Children With Special Healthcare Needs.

Background and objective Children with special healthcare needs are at an increased risk of oral health problems, including dental caries. Understanding the prevalence of dental caries, oral hygiene status, deft (decayed, extracted, filled teeth) index, and oral hygiene habits in this population is crucial for effective oral healthcare planning and interventions. The aim of this study was to assess the prevalence of dental caries, oral hygiene status, deft index, and oral hygiene habits among children aged 4-15 years with special healthcare needs in Jodhpur District, Rajasthan, India. Methods A cross-sectional study was conducted among 124 children from various, government and non-governmental organizations (NGO)-run special schools. Data on dental caries, oral hygiene status, deft index, and oral hygiene habits were collected using standardized tools and techniques. Descriptive statistics, including frequencies and percentages, were used to analyze the data. Results The prevalence of dental caries among children with special healthcare needs was 65%. The severity of dental caries varied, with 40% classified as mild, 20% as moderate, and 5% as severe. Additionally, 75% of the children exhibited poor oral hygiene, as indicated by the oral hygiene status assessment. The mean deft index score was 2.8, indicating an average dental caries experience among the participants. Regarding oral hygiene habits, 60% reported brushing their teeth once a day, while 40% reported brushing twice a day. However, a significant proportion (70%) reported non-fluoride use, and 55% stated they did not perform regular flossing. Conclusion This study highlights a high prevalence of dental caries, poor oral hygiene status, and suboptimal oral hygiene habits among children with special healthcare needs in Jodhpur District. The findings emphasize the need for targeted interventions focusing on preventive measures, oral health education, and improving access to oral healthcare for this vulnerable population. Further research with larger sample sizes and longitudinal study designs is warranted to validate these findings and develop effective strategies for enhancing oral health outcomes in children with special healthcare needs.

mTORC2-NDRG1-CDC42 axis couples fasting to mitochondrial fission.

Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at serine 336 sustains mitochondrial fission and respiratory sufficiency. Time-lapse imaging shows that NDRG1, but not the phosphorylation-deficient NDRG1Ser336Ala mutant, engages with mitochondria to facilitate fission in control cells, as well as in those lacking DRP1. Using proteomics, a small interfering RNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase CDC42 and effectors and regulators of CDC42 to orchestrate fission. Accordingly, RictorKO, NDRG1Ser336Ala mutants and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.

Administration of Metabiotics Extracted From Probiotic Lactobacillus rhamnosus MD 14 Inhibit Experimental Colorectal Carcinogenesis by Targeting Wnt/ß-Catenin Pathway.

Background and Objective: The cellular microenvironment, diet, and lifestyle play a key role in the occurrence of colorectal cancer. Due to its rising trend, attempts are being made to devise novel biointerventions as adjunct to conventional therapies to prevent this deadly disease. "Metabiotics," the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. Although beneficial attributes of metabiotics have been elucidated in vitro, yet their anticancer mechanism in vivo needs to be explored. Thus, the present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis. Materials and Methods: Sprague-Dawley rats were daily administered with low, medium, and high dose of metabiotic extract orally along with a single dose of weekly intraperitoneal injection of 1,2-dimethylhydrazine up to 6 weeks and monitored for the markers of early colon carcinogenesis. Results: It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, ß-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology. Conclusions: It can be suggested that metabiotics modulate experimental colorectal cancer and could be used as a promising alternative of probiotics, particularly in immunocompromised individuals.

Isolation, characterization and identification of antigenotoxic and anticancerous indigenous probiotics and their prophylactic potential in experimental colon carcinogenesis.

Colorectal cancer, the third most commonly diagnosed cancer, is a lifestyle disease where diet and gut microbiome contribute intricately in its initiation and progression. Prophylactic bio-interventions mainly probiotics offer an alternate approach towards reducing or delaying its progression. Therefore, the present study was designed wherein a robust protocol for the isolation, characterization, and identification of indigenous probiotics having antigenotoxic and anticancerous activity was followed along with their prophylactic potential assessment in early experimental colorectal carcinogenesis. Among forty-six isolated lactic acid bacterial strains, only three were selected on the basis of antigenotoxicity against N,N-Dimethyl dihydrazine dihydrochloride and 4-Nitroquinoline 1-oxide and probiotic attributes. All three selected probiotic strains exhibited anticancerous potential as is evident by the reduced Aberrant Crypt Foci, reduced fecal pH, enhanced fecal lactic acid bacteria and altered fecal enzymes (ß-glucuronidase, nitroreductase, ß-glucosidase) that modulated gut microbiota and microenvironment resulting into restored histoarchitecture of the colon. The results are a clear indicator of the prophylactic potential of selected indigenous probiotics which may be used as an alternative prophylactic biological therapy against colon carcinogenesis particularly in highly susceptible individuals.

Prophylactic Potential of Synbiotic (Lactobacillus casei and Inulin) in Malnourished Murine Giardiasis: an Immunological and Ultrastructural Study.

Giardiasis is a re-emerging infectious disease with outbreaks reported globally specially in children and malnourished individuals leading to malabsorption, growth retardation, and severe diarrhea. Thus, in the present study, prophylactic administration of synbiotic as the functional food was used to assess its antigiardial potential in malnourished murine giardiasis. Interestingly, prior administration of synbiotic (Lactobacillus casei + inulin) even to malnourished-Giardia-infected mice led to increased body mass, small intestine mass, lactobacilli counts, and reduced severity of giardiasis as evident by decreased cyst and trophozoite counts. Synbiotic therapy further boosted the innate and acquired immune response resulting into increase in nitric oxide, antigiardial secretory IgA and IgG antibody levels along with IL-6 and IL-10 cytokines, and decreased levels of inflammatory TNF-α cytokine in both serum and intestinal fluid in malnourished-synbiotic-Giardia-infected mice compared with malnourished-Giardia-infected mice. More specifically, histopathological and scanning electron microscopy analysis of the small intestine also confirmed the modulatory potentials of synbiotic in malnourished-synbiotic-Giardia mice which had less cellular and mucosal damage compared with severely damaged, mummified, and blunted villi in malnourished-Giardia-infected mice. Taken together, this is the first experimental study to report that prior supplementation of synbiotic restored the gut morphology and improved the immune status of the malnourished-Giardia-infected mice, and could be considered as the prophylactic adjunct therapy for malnourished individuals.

Metabiotics: One Step ahead of Probiotics; an Insight into Mechanisms Involved in Anticancerous Effect in Colorectal Cancer.

Colorectal cancer is closely associated with environment, diet and lifestyle. Normally it is treated with surgery, radiotherapy or chemotherapy but increasing systemic toxicity, resistance and recurrence is prompting scientists to devise new potent and safer alternate prophylactic or therapeutic strategies. Among these, probiotics, prebiotics, synbiotics, and metabiotics are being considered as the promising candidates. Metabiotics or probiotic derived factors can optimize various physiological functions of the host and offer an additional advantage to be utilized even in immunosuppressed individuals. Interestingly, anti colon cancer potential of probiotic strains has been attributable to metabiotics that have epigenetic, antimutagenic, immunomodulatory, apoptotic, and antimetastatic effects. Thus, it's time to move one step further to utilize metabiotics more smartly by avoiding the risks associated with probiotics even in certain normal/or immuno compromised host. Here, an attempt is made to provide insight into the adverse effects associated with probiotics and beneficial aspects of metabiotics with main emphasis on the modulatory mechanisms involved in colon cancer.

Symptomatic posterior fossa and supratentorial subdural hygromas as a rare complication following foramen magnum decompression for Chiari malformation Type I.

Symptomatic subdural hygroma due to foramen magnum decompression for Chiari malformation Type I is extremely rare. The authors present their experience with 2 patients harboring such lesions and discuss treatment issues. They conclude that the possibility of subdural hygromas should be considered in all patients presenting with increased intracranial tension following foramen magnum decompression for Chiari malformation Type I. Immediate neuroimaging and appropriate surgical intervention provides a good outcome.

A single institution series of cavernomas of the brainstem.

We retrospectively analyzed a series of patients with brainstem cavernomas of the medulla, pons, or midbrain to attempt to define the natural history, indications for surgery, and outcome after surgical resection. Between 1993 and 2008, 52 patients with cavernomas of the brainstem presented to our institute and were managed either surgically or conservatively. Twenty-three patients underwent surgical excision using standard skull base approaches. Outcomes were correlated to the number of preoperative hemorrhages, location of the cavernoma, timing of surgery in relation to the hemorrhage and the preoperative neurological status. Nine patients improved after surgery, 12 deteriorated and two died. In the conservatively managed group, 15 patients had a good outcome, 11 deteriorated and one died. Multiple hemorrhages, poor preoperative neurological status and surgery during the acute phase were predictive of the surgical outcome. Excision of brainstem cavernomas should be considered in patients with symptomatic hemorrhages whose lesions approach the pial surface. Patients with minimal stable neurologic deficits without recurrent bleeds should be managed conservatively.